Scaling up and implementing the digital Survivorship Passport tool in routine clinical care - The European multidisciplinary PanCareSurPass project.

BACKGROUND: Childhood cancer survivors (CCS), of whom there are about 500,000 living in Europe, are at an increased risk of developing health problems [1-6] and require lifelong Survivorship Care. There are information and knowledge gaps among CCS and healthcare providers (HCPs) about requirements for Survivorship Care [7-9] that can be addressed by the Survivorship Passport (SurPass), a digital tool providing CCS and HCPs with a comprehensive summary of past treatment and tailored recommendations for Survivorship Care. The potential of the SurPass to improve person-centred Survivorship Care has been demonstrated previously [10,11]. METHODS: The EU-funded PanCareSurPass project will develop an updated version (v2.0) of the SurPass allowing for semi-automated data entry and implement it in six European countries (Austria, Belgium, Germany, Italy, Lithuania and Spain), representative of three infrastructure healthcare scenarios typically found in Europe. The implementation study will investigate the impact on person-centred care, as well as costs and processes of scaling up the SurPass. Interoperability between electronic health record systems and SurPass v2.0 will be addressed using the Health Level Seven (HL7) International interoperability standards. RESULTS: PanCareSurPass will deliver an interoperable digital SurPass with comprehensive evidence on person-centred outcomes, technical feasibility and health economics impacts. An Implementation Toolkit will be developed and freely shared to promote and support the future implementation of SurPass across Europe. CONCLUSIONS: PanCareSurPass is a novel European collaboration that will improve person-centred Survivorship Care for CCS across Europe through a robust assessment of the implementation of SurPass v2.0 in different healthcare settings.

European recommendations for short-term surveillance of health problems in childhood, adolescent and young adult cancer survivors from the end of treatment to 5 years after diagnosis: a PanCare guideline.

PURPOSE: Childhood, adolescent and young adult (CAYA) cancer survivors require ongoing surveillance for health problems from the end of cancer treatment throughout their lives. There is a lack of evidence-based guidelines on optimal surveillance strategies for the period from the end of treatment to 5 years after diagnosis. We aimed to address this gap by developing recommendations for short-term surveillance of health problems based on existing long-term follow-up (LTFU) care guidelines. METHODS: The guideline working group, consisting of healthcare professionals, parents and survivor representatives from 10 countries, worked together to identify relevant health problems that may occur in survivors between the end of treatment and 5 years after diagnosis and to develop recommendations for short-term surveillance of health problems. The recommendations were drawn from existing LTFU guidelines and adapted where necessary based on clinical expertise. RESULTS: The working group developed 44 recommendations for short-term surveillance of health problems, which were divided into four categories based on the level of surveillance required: awareness only (n = 11), awareness, history and/or physical examination without surveillance test (n = 15), awareness, history and/or physical examination with potential surveillance test (n = 1) and awareness, history and/or physical examination with surveillance test (n = 17). CONCLUSION: The development of a guideline for short-term surveillance of health problems fills a critical gap in survivorship care for CAYA cancer survivors, providing much-needed support immediately after treatment up to 5 years after diagnosis. IMPLICATIONS FOR CANCER SURVIVORS: This guideline will support healthcare professionals to provide appropriate follow-up care and improve the quality of life of CAYA cancer survivors.

Evaluating the feasibility, effectiveness and costs of implementing person-centred follow-up care for childhood cancer survivors in four European countries: the PanCareFollowUp Care prospective cohort study protocol.

INTRODUCTION: Long-term survival after childhood cancer often comes at the expense of late, adverse health conditions. However, survivorship care is frequently not available for adult survivors in Europe. The PanCareFollowUp Consortium therefore developed the PanCareFollowUp Care Intervention, an innovative person-centred survivorship care model based on experiences in the Netherlands. This paper describes the protocol of the prospective cohort study (Care Study) to evaluate the feasibility and the health economic, clinical and patient-reported outcomes of implementing PanCareFollowUp Care as usual care in four European countries. METHODS AND ANALYSIS: In this prospective, longitudinal cohort study with at least 6 months of follow-up, 800 childhood cancer survivors will receive the PanCareFollowUp Care Intervention across four study sites in Belgium, Czech Republic, Italy and Sweden, representing different healthcare systems. The PanCareFollowUp Care Intervention will be evaluated according to the Reach, Effectiveness, Adoption, Implementation and Maintenance framework. Clinical and research data are collected through questionnaires, a clinic visit for multiple medical assessments and a follow-up call. The primary outcome is empowerment, assessed with the Health Education Impact Questionnaire. A central data centre will perform quality checks, data cleaning and data validation, and provide support in data analysis. Multilevel models will be used for repeated outcome measures, with subgroup analysis, for example, by study site, attained age, sex or diagnosis. ETHICS AND DISSEMINATION: This study will be conducted in accordance with the guidelines of Good Clinical Practice and the Declaration of Helsinki. The study protocol has been reviewed and approved by all relevant ethics committees. The evidence and insights gained by this study will be summarised in a Replication Manual, also including the tools required to implement the PanCareFollowUp Care Intervention in other countries. This Replication Manual will become freely available through PanCare and will be disseminated through policy and press releases. TRIAL REGISTRATION NUMBER: Netherlands Trial Register (NL8918; https://www.trialregister.nl/trial/8918).

QUARTET: A SIOP Europe project for quality and excellence in radiotherapy and imaging for children and adolescents with cancer.

The European Society for Paediatric Oncology (SIOPE) Radiation Oncology Working Group presents the QUARTET Project: a centralised quality assurance programme designed to standardise care and improve the quality of radiotherapy and imaging for international clinical trials recruiting children and adolescents with cancer throughout Europe. QUARTET combines the paediatric radiation oncology expertise of SIOPE with the infrastructure and experience of the European Organisation for Research and Treatment of Cancer to deliver radiotherapy quality assurance programmes for large, prospective, international clinical trials. QUARTET-affiliated trials include children and adolescents with brain tumours, neuroblastoma, sarcomas including rhabdomyosarcoma, and renal tumours including Wilms' tumour. With nine prospective clinical trials and two retrospective studies within the active portfolio in March 2022, QUARTET will collect one of the largest repositories of paediatric radiotherapy and imaging data, support the clinical assessment of radiotherapy, and evaluate the role and benefit of radiotherapy quality assurance for this cohort of patients within the context of clinical trials.

Impact of era of diagnosis on cause-specific late mortality among 77 423 five-year European survivors of childhood and adolescent cancer: The PanCareSurFup consortium.

Late mortality of European 5-year survivors of childhood or adolescent cancer has dropped over the last 60 years, but excess mortality persists. There is little information concerning secular trends in cause-specific mortality among older European survivors. PanCareSurFup pooled data from 12 cancer registries and clinics in 11 European countries from 77 423 five-year survivors of cancer diagnosed before age 21 between 1940 and 2008 followed for an average age of 21 years and a total of 1.27 million person-years to determine their risk of death using cumulative mortality, standardized mortality ratios (SMR), absolute excess risks (AER), and multivariable proportional hazards regression analyses. At the end of follow-up 9166 survivors (11.8%) had died compared to 927 expected (SMR 9.89, 95% confidence interval [95% CI] 9.69-10.09), AER 6.47 per 1000 person-years, (95% CI 6.32-6.62). At 60 to 68 years of attained age all-cause mortality was still higher than expected (SMR = 2.41, 95% CI 1.90-3.02). Overall cumulative mortality at 25 years from diagnosis dropped from 18.4% (95% CI 16.5-20.4) to 7.3% (95% CI 6.7-8.0) over the observation period. Compared to the diagnosis period 1960 to 1969, the mortality hazard ratio declined for first neoplasms (P for trend <.0001) and for infections (P < .0001); declines in relative mortality from second neoplasms and cardiovascular causes were less pronounced (P = .1105 and P = .0829, respectively). PanCareSurFup is the largest study with the longest follow-up of late mortality among European childhood and adolescent cancer 5-year survivors, and documents significant mortality declines among European survivors into modern eras. However, continuing excess mortality highlights survivors' long-term care needs.

The European multistakeholder PanCareFollowUp project: novel, person-centred survivorship care to improve care quality, effectiveness, cost-effectiveness and accessibility for cancer survivors and caregivers.

BACKGROUND: The majority of childhood cancer survivors are at risk of treatment-related adverse health outcomes. Survivorship care to mitigate these late effects is endorsed, but it is not available for many adult survivors of childhood cancer in Europe. The PanCareFollowUp project was initiated to improve their health and quality of life (QoL) by facilitating person-centred survivorship care. METHODS: The PanCareFollowUp consortium was established in 2018, consisting of 14 project partners from ten European countries, including survivor representatives. The consortium will develop two PanCareFollowUp Interventions, including a person-centred guideline-based model of care (Care Intervention) and eHealth lifestyle coaching (Lifestyle Intervention). Their development will be informed by several qualitative studies and systematic reviews on barriers and facilitators for implementation and needs and preferences of healthcare providers (HCPs) and survivors. Implementation of the PanCareFollowUp Care Intervention as usual care will be evaluated prospectively among 800 survivors from Belgium, Czech Republic, Italy and Sweden for survivor empowerment, detection of adverse health conditions, satisfaction among survivors and HCPs, cost-effectiveness and feasibility. The feasibility of the PanCareFollowUp Lifestyle Intervention will be evaluated in the Netherlands among 60 survivors. RESULTS: Replication manuals, allowing for replication of the PanCareFollowUp Care and Lifestyle Intervention, will be published and made freely available after the project. Moreover, results of the corresponding studies are expected within the next five years. CONCLUSIONS: The PanCareFollowUp project is a novel European collaboration aiming to improve the health and QoL of all survivors across Europe by developing and prospectively evaluating the person-centred PanCareFollowUp Care and Lifestyle Interventions.

PRIMAGE project: predictive in silico multiscale analytics to support childhood cancer personalised evaluation empowered by imaging biomarkers.

PRIMAGE is one of the largest and more ambitious research projects dealing with medical imaging, artificial intelligence and cancer treatment in children. It is a 4-year European Commission-financed project that has 16 European partners in the consortium, including the European Society for Paediatric Oncology, two imaging biobanks, and three prominent European paediatric oncology units. The project is constructed as an observational in silico study involving high-quality anonymised datasets (imaging, clinical, molecular, and genetics) for the training and validation of machine learning and multiscale algorithms. The open cloud-based platform will offer precise clinical assistance for phenotyping (diagnosis), treatment allocation (prediction), and patient endpoints (prognosis), based on the use of imaging biomarkers, tumour growth simulation, advanced visualisation of confidence scores, and machine-learning approaches. The decision support prototype will be constructed and validated on two paediatric cancers: neuroblastoma and diffuse intrinsic pontine glioma. External validation will be performed on data recruited from independent collaborative centres. Final results will be available for the scientific community at the end of the project, and ready for translation to other malignant solid tumours.

Care of adolescents and young adults with cancer in Asia: results of an ESMO/SIOPE/SIOP Asia survey.

BACKGROUND: Adolescents and young adults (AYAs) with cancer require dedicated management encompassing both adult and paediatric cancer services. Following a European survey, the European Society for Medical Oncology, the European Society for Paediatric Oncology and the Asian continental branch of International Society of Paediatric Oncology undertook a similar survey to assess AYA cancer care across Asia. METHODS: A link to the online survey was sent to healthcare professionals (HCPs) in Asia interested in AYA cancer care. Questions covered the demographics and training of HCPs, their understanding of AYA definition, availability and access to specialised AYA services, the support and advice offered during and after treatment, and factors of treatment non-compliance. RESULTS: We received 268 responses from 22 Asian countries. There was a striking variation in the definition of AYA (median lower age 15 years, median higher age 29 years). The majority of the respondents (78%) did not have access to specialised cancer services and 73% were not aware of any research initiatives for AYA. Over two-thirds (69%) had the option to refer their patients for psychological and/or nutritional support and most advised their patients on a healthy lifestyle. Even so, 46% did not ask about smokeless tobacco habits and only half referred smokers to a smoking cessation service. Furthermore, 29% did not promote human papillomavirus vaccination for girls and 17% did not promote hepatitis B virus vaccination for high-risk individuals. In terms of funding, 69% reported governmental insurance coverage, although 65% reported that patients self-paid, at least partially. Almost half (47%) reported treatment non-compliance or abandonment as an issue, attributed to financial and family problems (72%), loss of follow-up (74%) and seeking of alternative treatments (77%). CONCLUSIONS: Lack of access to and suboptimal delivery of AYA-specialised cancer care services across Asia pose major challenges and require specific interventions.

The 'Survivorship Passport' for childhood cancer survivors.

BACKGROUND: Currently, there are between 300,000 and 500,000 childhood cancer survivors (CCSs) in Europe. A significant proportion is at high risk, and at least 60% of them develop adverse health-related outcomes that can appear several years after treatment completion. Many survivors are unaware of their personal risk, and there seems to be a general lack of information among healthcare providers about pathophysiology and natural history of treatment-related complications. This can generate incorrect or delayed diagnosis and treatments. METHOD: The Survivorship Passport (SurPass) consists of electronic documents, which summarise the clinical history of the childhood or adolescent cancer survivor. It was developed by paediatric oncologists of the PanCare and SIOPE networks and IT experts of Cineca, together with parents, patients, and survivors' organisations within the European Union-funded European Network for Cancer research in Children and Adolescents. It consists of a template of a web-based, simply written document, translatable in all European languages, to be given to each CCS. The SurPass provides a summary of each survivor's clinical history, with detailed information about the original cancer and of treatments received, together with personalised follow-up and screening recommendations based on guidelines published by the International Guidelines Harmonization Group and PanCareSurFup. RESULTS: The SurPass data schema contains a maximum of 168 variables and uses internationally approved nomenclature, except for radiotherapy fields, where a new classification was defined by radiotherapy experts. The survivor-specific screening recommendations are mainly based on treatment received and are automatically suggested, thanks to built-in algorithms. These may be adapted and further individualised by the treating physician in case of special disease and survivor circumstances. The SurPass was tested at the Istituto Giannina Gaslini, Italy, and received positive feedback. It is now being integrated at the institutional, regional and national level. CONCLUSIONS: The SurPass is potentially an essential tool for improved and more harmonised follow-up of CCS. It also has the potential to be a useful tool for empowering CCSs to be responsible for their own well-being and preventing adverse events whenever possible. With sufficient commitment on the European level, this solution should increase the capacity to respond more effectively to the needs of European CCS.

The care of adolescents and young adults with cancer: results of the ESMO/SIOPE survey.

INTRODUCTION: Adolescents and young adults (AYA) with cancer require dedicated clinical management and care. Little is known about the training and practice of European healthcare providers in regard to AYA and the availability of specialised services. METHODS: A link to an online survey was sent to members of the European Society for Medical Oncology (ESMO) and the European Society for Paediatric Oncology (SIOPE). The link was also sent to ESMO National Representatives and circulated to other European oncology groups. Questions covered the demographics and clinical training of respondents, their definition of AYA, education about AYA cancer, access to specialised clinical and supportive care, research and further education. Data from Europe were analysed by region. RESULTS: Three hundred tweenty two questionnaires were submitted and we focused on data from the 266 European healthcare professionals. Responses revealed considerable variation both within and between countries in the definition of AYA. Over two-thirds of respondents did not have access to specialised centres for AYA (67%), were not aware of research initiatives focusing on AYA with cancer (69%) and had no access to specialist services for managing the late effects of treatment (67%). The majority of the respondents were able to refer AYA patients to professional psychological support and specialised social workers. However, more than half had no access to an age-specialised nurse or specialised AYA education. Overall, 38% of respondents reported that their AYA patients did not have access to fertility specialists. This figure was 76% in Eastern Europe. Lack of specialised AYA care was particularly evident in Eastern and South-Eastern Europe. CONCLUSION: There is important underprovision and inequity of AYA cancer care across Europe. Improving education and research focused on AYA cancer care should be a priority.

European Survey on Standards of Care in paediatric oncology centres.

BACKGROUND: In recent years, the European Commission has supported an increased focus on rare cancers in order to improve quality of care, disseminate best practice and set up networks to improve access that is essential to continued progress. At European Union (EU) conference in 2009, an agreement was reached to create a 'European Standard of Care for Children with Cancer'. In 2013, the European Paediatric Oncology Society launched a Europe-wide survey in order to assess the implementation of the Standards. METHODS: Representative experts from 36 countries, including 27 EU members, were invited to complete a questionnaire describing the quality of treatment and care received by young cancer patients in their country, together with the characteristics of the health care infrastructure and paediatric haematology-oncology (PHO) teams. FINDINGS: Thirty-five European countries provided comprehensive responses. Within the responding countries, 341 PHO centres were identified. Only 18 countries consider they have full diagnostic services, all necessary drugs and supportive care. The annual incidence rate is approximately 146.1 new cancer cases/million children and adolescents. In 24 countries, paediatric haematology and oncology is officially recognised as a specific qualification. A total of 1178 specialists certified in PHO are currently working in Europe. Finally, 31 (88.6%) countries provide a multidisciplinary palliative care for terminally ill children. INTERPRETATION: This survey provides quantitative data that demonstrate the current healthcare inequalities for children and adolescents with cancer in Europe. This variability in care provision and quality is likely to underlie the variation in childhood cancer survival rate in these countries.

Challenges for children and adolescents with cancer in Europe: the SIOP-Europe agenda.

In Europe, 6,000 young people die of cancer yearly, the commonest disease causing death beyond the age of 1 year. In addition, 300,000-500,000 European citizens are survivors of a childhood cancer and up to 30% of them have severe long-term sequelae of their treatment. Increasing both cure and quality of cure are the two goals of the European paediatric haematology/oncology community. SIOPE coordinates and facilitates research, care and training which are implemented by the 18 European study groups and 23 national paediatric haematology/oncology societies. SIOPE is the European branch of the International Society of Paediatric Oncology and one of the six founding members of the European Cancer Organisation. SIOPE is preparing its strategic agenda to assure long-term sustainability of clinical and translational research in paediatric malignancies over the next 15 years. SIOPE tackles the issues of equal access to standard care and research across Europe and improvement of long term follow up. SIOPE defined a comprehensive syllabus for training European specialists. A strong partnership with parent, patient and survivor organisations is being developed to successfully achieve the goals of this patient-centred agenda. SIOPE is advocating in the field of EU policies, such as the Clinical Trials Regulation and the Paediatric Medicine Regulation, to warrant that the voice of young people is heard and their needs adequately addressed. SIOPE and the European community are entirely committed to the global agenda against childhood cancers to overcome the challenges to increasing both cure and quality of cure of young people with cancer.

Towards reducing inequalities: European Standards of Care for Children with Cancer.

Despite the increase of cure rates in the treatment of children with cancer there is a significant discrepancy in the outcome within Europe. Data are showing us that there is a difference of 20% in outcomes for young people with cancer when comparing North and Western Europe with Central and Eastern Europe. One of the most important necessities, in order to be able to have comparable results and equitable outcomes about inequalities, is to have the Principle Treatment Centres, meeting a minimum level of standards and being accessible to continuously updated 'best practice'. The European Society of Paediatric Oncology (SIOPE) has initiated a study in order to monitor the current situation of the European Standards of Paediatric Oncology Centres. The results of the study showed disparities of Standards of Care in the Treatment Centres across Europe. Therefore SIOPE initiated a project aimed at improving the Quality-of-Care of children and adolescents with cancer and to assess the relevant organisational aspects within paediatric oncology. At the first European Union (EU) Conference in Warsaw 2009, an agreement was obtained from all involved stakeholders to initiate the creation of Pan-European guidelines entitled 'European Standards of Care for Children with Cancer'. The guidelines outlined in this document represent the minimum standards of care that should be implemented at the EU level. Describing the different aspects of Care over 15 chapters and available in more than 16 different EU languages these guidelines are used as tools for both professionals and parent/patients groups in order to advocate 'improved standards across EU'.